Modulating the Allergen-Specific Immune Response to Achieve Remission of Food Allergy Through Oral Immunotherapy

Food allergies represent a significant global health issue, affecting approximately 2% of children and up to 10% of 1-year-old infants. Oral immunotherapy has emerged as a promising treatment for food allergies. Oral immunotherapy (OIT) is effective at inducing desensitization, defined as a temporary increase in reaction threshold to food allergens, and a low-dose OIT approach (Palforzia) is now approved in several regions, including the United States, the United Kingdom, and the European Union. However, the ability for OIT to induce sustained unresponsiveness or remission, defined as the ability to tolerate the allergen without ongoing treatment or avoidance, is less certain and may depend on the OIT dosing regimen that is applied; for example, high-dose peanut OIT regimens have been shown to induce remission in ~30-74% of treated patients. Desensitization offers temporary protection against accidental exposure to allergens; however, drawbacks include the need for indefinite maintenance dosing and continuing allergen avoidance. Additionally, data show that desensitization does not improve health-related quality of life compared with a placebo. In contrast, remission allows participants to discontinue treatment, eat the allergen freely, and leads to substantial improvement in quality of life. This chapter examines the immune mechanisms driving food allergy pathogenesis and the mechanisms that support remission following OIT. Gene expression studies in patient samples from clinical OIT trials have provided insight into the immune pathways involved in redirecting the allergic response toward tolerance, with changes in allergen-reactive T cells, B cells, and baseline signatures. This chapter aims to provide an overview of the immune changes underlying food allergy and the immune mechanisms of OIT that lead to remission of allergy.